Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis

Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxic...

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Detalhes bibliográficos
Autores: Ardanaz, Carlos G., de la Cruz, Aida, Minhas, Paras S., Hernández-Martín, Nira, Pozo, Miguel Ángel, Valdecantos, M. Pilar, Valverde, Ángela M., Villa-Valverde, Palmira, Elizalde-Horcada, Marcos, Puerta, Elena, Ramírez, María J., Ortega, Jorge E., Urbiola, Ainhoa, Ederra, Cristina, Ariz, Mikel, Ortiz-De-Solórzano, Carlos, Fernández-Irigoyen, Joaquín, Santamaría, Enrique, Karsenty, Gerard, Brüning, Jens C., Solas, Maite
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universidad Francisco de Vitoria
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/7308
Acesso em linha:https://hdl.handle.net/10641/7308
Access Level:acceso abierto
Palavra-chave:General
SDG 3 - Good Health and Well-being
Journal Article
Yes
yes
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spelling Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasisArdanaz, Carlos G.de la Cruz, AidaMinhas, Paras S.Hernández-Martín, NiraPozo, Miguel ÁngelValdecantos, M. PilarValverde, Ángela M.Villa-Valverde, PalmiraElizalde-Horcada, MarcosPuerta, ElenaRamírez, María J.Ortega, Jorge E.Urbiola, AinhoaEderra, CristinaAriz, MikelOrtiz-De-Solórzano, CarlosFernández-Irigoyen, JoaquínSantamaría, EnriqueKarsenty, GerardBrüning, Jens C.Solas, MaiteGeneralSDG 3 - Good Health and Well-beingJournal ArticleYesyesAstrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1ΔGFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Mechanistically, we observed that GLUT1-deficient astrocytes exhibited increased insulin receptor-dependent ATP release, and that both astrocyte insulin signaling and brain purinergic signaling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its depletion triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis, and cognitive function.Facultad de Ciencias Experimentales20242024-10-1820242024-10-18journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/7308reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad Francisco de VitoriaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/73082026-06-11T12:44:57Z
dc.title.none.fl_str_mv Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
title Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
spellingShingle Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
Ardanaz, Carlos G.
General
SDG 3 - Good Health and Well-being
Journal Article
Yes
yes
title_short Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
title_full Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
title_fullStr Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
title_full_unstemmed Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
title_sort Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
dc.creator.none.fl_str_mv Ardanaz, Carlos G.
de la Cruz, Aida
Minhas, Paras S.
Hernández-Martín, Nira
Pozo, Miguel Ángel
Valdecantos, M. Pilar
Valverde, Ángela M.
Villa-Valverde, Palmira
Elizalde-Horcada, Marcos
Puerta, Elena
Ramírez, María J.
Ortega, Jorge E.
Urbiola, Ainhoa
Ederra, Cristina
Ariz, Mikel
Ortiz-De-Solórzano, Carlos
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Karsenty, Gerard
Brüning, Jens C.
Solas, Maite
author Ardanaz, Carlos G.
author_facet Ardanaz, Carlos G.
de la Cruz, Aida
Minhas, Paras S.
Hernández-Martín, Nira
Pozo, Miguel Ángel
Valdecantos, M. Pilar
Valverde, Ángela M.
Villa-Valverde, Palmira
Elizalde-Horcada, Marcos
Puerta, Elena
Ramírez, María J.
Ortega, Jorge E.
Urbiola, Ainhoa
Ederra, Cristina
Ariz, Mikel
Ortiz-De-Solórzano, Carlos
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Karsenty, Gerard
Brüning, Jens C.
Solas, Maite
author_role author
author2 de la Cruz, Aida
Minhas, Paras S.
Hernández-Martín, Nira
Pozo, Miguel Ángel
Valdecantos, M. Pilar
Valverde, Ángela M.
Villa-Valverde, Palmira
Elizalde-Horcada, Marcos
Puerta, Elena
Ramírez, María J.
Ortega, Jorge E.
Urbiola, Ainhoa
Ederra, Cristina
Ariz, Mikel
Ortiz-De-Solórzano, Carlos
Fernández-Irigoyen, Joaquín
Santamaría, Enrique
Karsenty, Gerard
Brüning, Jens C.
Solas, Maite
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias Experimentales
dc.subject.none.fl_str_mv General
SDG 3 - Good Health and Well-being
Journal Article
Yes
yes
topic General
SDG 3 - Good Health and Well-being
Journal Article
Yes
yes
description Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1ΔGFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Mechanistically, we observed that GLUT1-deficient astrocytes exhibited increased insulin receptor-dependent ATP release, and that both astrocyte insulin signaling and brain purinergic signaling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its depletion triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis, and cognitive function.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-10-18
2024
2024-10-18
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/7308
url https://hdl.handle.net/10641/7308
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad Francisco de Vitoria
instname_str Universidad Francisco de Vitoria
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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